Compound Tied to Cognitive Deficits in Schizophrenia

WEDNESDAY Nov. 19, 2008 -- Elevated brain levels of a compound called kynurenic acid are associated with problem-solving deficits in people with schizophrenia, according to U.S. researchers.

Drugs that suppress kynurenic acid might be used in conjunction with antipsychotic drugs to treat cognitive impairments, the most resistant symptoms in schizophrenia patients, the researchers said.

"We've got this core cluster of symptoms that is the Achilles' heel for these individuals, and we're not really doing a good job of treating them," principal investigator John P. Bruno, professor of psychology, psychiatry and neuroscience at Ohio State University, explained in a university news release.

Kynurenic acid is present in all human brains and has useful functions. However, an excessive amount of the compound interferes with other chemical processes involved in the ability to pay attention and think strategically under changing circumstances, said Bruno and colleagues, who conducted their research in rats.

A group of rats was given a compound that stimulated excess production of kynurenic acid and compared to a control group of normal rats. Both groups were tested on their ability to make decisions when subjected to changing conditions. Only 28 percent of the rats with elevated kynurenic acid were able to solve problems to receive a food reward, compared with 100 percent of the normal rats.

Increased levels of kynurenic acid exacerbate an existing problem in people with schizophrenia, who have lower-than-normal levels and activity of two neurotransmitters (acetylcholine and glutamate) critical to normal cognition, the researcher said. The activity of these neurotransmitters is partially regulated by a class of proteins called alpha-7 receptors. Excess levels of kynurenic acid inhibit the action of alpha-7 receptors.

"So, we've already got problems with these neurotransmitters, and then to make matters worse, we've got all this extra kynurenic acid antagonizing the alpha-7 receptors, which just throws gasoline on the fire," Bruno said. "If we can design drugs that are able to inhibit the enzymes that are responsible for overproducing kynurenic acid, we may improve cognitive performance in these patients."

The research was to be presented Nov. 18 at the Society for Neuroscience meeting in Washington, D.C.

Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment.